The regulation of dopamine transmission by metabotropic glutamate receptors

Receptor subtype nonselective metabotropic glutamate receptor (mGluR) agonists have been shown to regulate the release of dopamine. The eight mGluR subtypes have been pharmacologically categorized into three groups, and the present study used in vivo microdialysis to examine the capacity of mGluR subgroup-selective drugs to modulate the extracellular levels of dopamine in the nucleus accumbens. By administering the drugs in the dialysis buffer, it was found that the group 3 mGluR agonist L-amino-4-phosphonobutyrate produced a dose-dependent reduction in extracellular dopamine, whereas the group 1 agonist 3,5-dihydroxyphenylglycine was ineffective. The group 2 agonist (2S,1'R,2'R,3'R)-2-(2, 3-dicarboxycyclopropyl)glycine produced a reduction that was biphasic with respect to dose. The group 2/3 antagonist alpha-methyl-4-phosphnophenylglycine elicited a dose-dependent increase in extracellular dopamine that was antagonized by coperfusion with either the L-type calcium channel blocker diltiazem or the group 3 agonist L-amino-4-phosphonobutyrate. These data demonstrate that group 3 and to a lesser extent group 2 mGluR may presynaptically regulate dopamine release or reuptake. Moreover, there exists significant in vivo glutamatergic tone on group 2/3 mGluRs to suppress extracellular dopamine levels.